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Scientific Challenges and Solutions for Cultured Meat Manufacturing
Several key challenges remain in producing cultured meat including access to proprietary cell lines, high raw material cost, animal-source nutrients, and limited manufacturing scale. Despite this, immense progress has been made over the last decade.
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The rising environmental cost of cattle meat production, emergence of multi-drug resistant bacteria from overusing antibiotics in livestock, and pressure from supply chain disruptions during the COVID-19 pandemic are accelerating developments in cultured meat, a form of animal-free meat alternative. Cultured meat is also known as in vitro meat, lab grown meat, cultivated meat, or synthetic meat.
In 2013, Mark Post, PhD, professor at Maastricht University, unveiled the first cultured meat patty grown from cells on television. Seven years later in 2020, Singapore became the first country to approve lab grown chicken bites from Eat Just. As an industry, cultured meat is expected to reach a market size of about $570 million in 2025.
“Cultured meat has the potential to address all of the externalities associated with conventional industrial meat production—from environmental impacts and animal welfare considerations to public health risks associated with zoonotic disease and antibiotic resistance—while ensuring a scalable and secure production system to meet the anticipated growth in demand for animal protein,” says Liz Specht, director of science & technology at the Good Food Institute.
“Cultured meat also ultimately offers the opportunity to create meat products that are more well-defined, tunable, and potentially healthier than meat products today, which are constrained by the biological limitations of the domestic animals from which they are derived.”
Owing to advances in industrial-scale cell culture process, the production of cultured meat has been largely standardized. Typically stem cells are first seeded into extracellular matrix scaffolds usually made of edible biomaterials like collagen and chitin. To support cellular metabolic activities, culture media containing nutrients like glucose and sera are next added to the bioreactor where continual mechanical motion facilitates good diffusion of nutrients and oxygen into and removal of metabolic waste products from the cells. After about 2–8 weeks, the cells grow into tissue layers and can be harvested and packaged.
Challenges in cultured meat production
Several key challenges remain in producing cultured meat including access to (proprietary) cell lines, high raw material cost, animal-source nutrients, and limited manufacturing scale. Despite this, immense progress has been made over the last decade. Here, we discuss the challenges and solutions to deliver cultured meat from a lab bench to a dining table.
Cell lines are commonly used in the biotech industry for production of biological materials including viruses and proteins. For cultured meat, stem cells are used as they can divide indefinitely and can be differentiated into different types of lineages—just like meat from different organs. Adult stem cells can be sourced directly from the parts of animals such as muscles, liver, and adipose tissues. Alternatively, pluripotent stem cells can be obtained from embryos or de-differentiated from fibroblasts into induced pluripotent stem cells.
Emerging transgene-free technology such as microfluidics and nano-structures which can deliver genes at high throughput and efficiency are being developed to overcome this technical limitation. Hur and colleagues recently described an inexpensive (< $1) microfluidic system that makes use of cell stretching to delivery genes into stem cells at a scalable throughput of a million cells/min. Likewise, high aspect-ratio nano-structures can also facilitate efficient, minimally perturbative gene delivery into stem cells.
Second, cell line characterization is not well standardized which can adversely affect quality control. When cells divide more rapidly, there is a higher probability that their genetic content is not stable. For instance, during DNA replication, there can be copy number variations and large insertions or deletions that can lead to undesirable phenotypic and functional changes. Advanced techniques such as single cell genomic and epigenomic sequencing and transcriptomics can reveal differences even among cells belonging to the same cell line to understand stochastic heterogeneity in cells.
Culture conditions can also be modified and coupled with single cell sequencing methods to discover the roles of genes and their impact on cellular phenotypes. As the price of sequencing drops, data from these techniques would likely establish a benchmark to evaluate genetic stability of cell lines for quality control.
Biomaterial scaffold
Scaffolds are extracellular matrix materials that support the anchorage and physiological activities such as differentiation of stem cells. The biophysical properties of scaffolds are crucial to facilitate access to nutrients and oxygen while permitting diffusion of metabolic waste products. Tissue engineers have built on their knowledge in tissue engineering for wounds and organ regeneration for cultured meat production.
There are two general types of scaffold materials—naturally-derived or synthetic. Naturally-derived scaffolds like chitosan and cellulose are edible, biodegradable, food-safe, and cheap. However, as they are derived naturally, there is a greater variation in their properties such as molecular weight and degree of polymerization. This can lead to inconsistencies in how these scaffolds interact with cells. On the other hand, synthetic scaffolds can be chemically programmed into desirable materials with defined properties like porosity and ligand availability. However, as their synthesis process is more complex, the cost is higher and getting regulatory approval is also expected to be harder.
A proposed solution is a hybrid model where naturally-derived biomaterial is used as base material and a small amount of synthetic material is added to enhance the compatibility with cultured cells. Advanced manufacturing methods like 3D printing can also be used to “print” scaffolds with defined properties.
It is extremely difficult to create a thick tissue layer because there is little to no vascularization in cultured meat. Consequently, when the tissue layer becomes too thick, cells at the core of the tissue suffer from a lack of nutrients and oxygen. Computational analyses have been applied to understand the optimal scaffold pore size, topography, and material shape to facilitate vascularization in tissue layers and/or promote nutrient and waste production diffusion.
“First, plunge micro needle arrays into thick tissue layers or incorporate vasculature like perfusable features into scaffold or bioreactor design. Second, use cell-sheet tissue engineering approaches to grow thin enough sheets of tissues and then integrate them into food. Third, adopting bottom-up approach to engineer small tissue building blocks and integrate into food so there is no need to worry about the diffusion limit in thick layers,” says Yu.
Yu, however, stresses that, the dominant voice in the field is using a top-down approach where cells are being seeded into a large piece of scaffold and grown into thick tissue layers. “Based on my experience as a tissue engineer over the last few decades, I don’t foresee that we can use a top-down approach at a cost-effective manner for growing cultured meat,” he adds.
Growth media recipes
As cell lines divide rapidly, growth media needs to be able to supply them with high concentrations of essential nutrients including glucose, amino acids, and vitamins. Commercial growth media is costly, and a lack of better alternative has kept the prices of cultured meat high. In addition, while cultured meat is purported as an animal-free meat alternative, in reality, its production may still require animal source materials such fetal bovine sera. Sera is a complex mixture of multiple types of amino acids, lipids, inorganic mineral, and growth factors that cannot be easily or cheaply manufactured, and this has made it challenging for it to be replaced in cultured meat manufacturing.
Kuo et al., described a culture medium recipe containing fibroblast growth factor 2, transforming growth factor β3 and neuregulin 1 for induced pluripotent stem cells that can be produced with just 3% of the costs of commercial media. Importantly, the medium recipe was able to sustain more than 100 passages of cell division and weekend-free feeding without compromising the differentiation capacity of 34 different types of stem cells.
Through technological developments, researchers are also exploring ways to scale up production of recombinant proteins like growth factors at a lower cost using genetically engineered microbes, fungi, or plants to circumvent animal sources. There are also research groups who have develop growth culture media that is entirely void of serum. Kolkmann and colleagues developed a chemically-defined, serum-free media which supported bovine myoblast proliferation exponentially, albeit not as fast as media with 30% serum content.
Bioreactors provide controlled culture environment such as temperature, pH, and even mechanical motion to optimize cell growth. They are an important element in the cultured meat industry to achieve scalable production to meet consumer demand. Stephens et al., estimated that, for instance, to produce 1 kg of protein from muscle cells, 8 x 1012 cells would be needed and that would require a stirred tank bioreactor in the order of a few thousand liters.
Although bench-top bioreactors have so far been quite successful in meeting current demand for cultured meat, as the demand increases, greater innovation is warranted in bioreactor design. In addition, most commercial bioreactors are designed for growing suspension cells or cells anchored onto micro-carriers, and not scaffold materials with thick tissue layers. This makes it challenging to directly adapt available designs for cultured meat production due to system incompatibility like diffusion limits.
Nevertheless, past experiences can inform bioreactor designs for cultured meat manufacturing. For instance, it would be beneficial to introduce mechanical agitation such as stirring or wave rocking motion to improve nutrient diffusion. Perfusion bioreactors that continually supply nutrients and remove waste products are also better for growing thick tissue layers. Single-use bioreactors can also be considered to minimize contamination and for quicker and cheaper optimization of culture conditions.
The future of cultured meat
Cultured meat provides a hope that our society can become less reliant on animals for meat, thus reducing the environmental and health impact of animal farming. There are still major scientific challenges including developing quality cell lines, lowering the costs of growth media components, and designing bioreactors for growing thick tissue layers before cultured meat can become a common food product. Nevertheless, there is room for optimism.
“In the past few years, we have seen a rapid acceleration of interest in cultured meat research by academic researchers and startup companies. This emerging field is also increasingly capitalizing on the ability to work collaboratively on pre-competitive research angles that will accelerate the whole landscape. At the Good Food Institute, we facilitate seminars and collaborative networking opportunities and curate resources like research tools directory and directly fund research to address key knowledge gaps and develop open-access research tools,” says Specht.
Sophisticated technology in genetic engineering, biomaterial design and sequencing methods can offer effective technical solutions. Greater scientific solutions are also expected with increasing investments in the science of alternative food. Importantly, beyond the science, for cultured meat to become a common market commodity, challenges in regulations and consumer acceptance must still be overcome.
The post Scientific Challenges and Solutions for Cultured Meat Manufacturing appeared first on GEN - Genetic Engineering and Biotechnology News.
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Chinese migration to US is nothing new – but the reasons for recent surge at Southern border are
A gloomier economic outlook in China and tightening state control have combined with the influence of social media in encouraging migration.
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The brief closure of the Darien Gap – a perilous 66-mile jungle journey linking South American and Central America – in February 2024 temporarily halted one of the Western Hemisphere’s busiest migration routes. It also highlighted its importance to a small but growing group of people that depend on that pass to make it to the U.S.: Chinese migrants.
While a record 2.5 million migrants were detained at the United States’ southwestern land border in 2023, only about 37,000 were from China.
I’m a scholar of migration and China. What I find most remarkable in these figures is the speed with which the number of Chinese migrants is growing. Nearly 10 times as many Chinese migrants crossed the southern border in 2023 as in 2022. In December 2023 alone, U.S. Border Patrol officials reported encounters with about 6,000 Chinese migrants, in contrast to the 900 they reported a year earlier in December 2022.
The dramatic uptick is the result of a confluence of factors that range from a slowing Chinese economy and tightening political control by President Xi Jinping to the easy access to online information on Chinese social media about how to make the trip.
Middle-class migrants
Journalists reporting from the border have generalized that Chinese migrants come largely from the self-employed middle class. They are not rich enough to use education or work opportunities as a means of entry, but they can afford to fly across the world.
According to a report from Reuters, in many cases those attempting to make the crossing are small-business owners who saw irreparable damage to their primary or sole source of income due to China’s “zero COVID” policies. The migrants are women, men and, in some cases, children accompanying parents from all over China.
Chinese nationals have long made the journey to the United States seeking economic opportunity or political freedom. Based on recent media interviews with migrants coming by way of South America and the U.S.’s southern border, the increase in numbers seems driven by two factors.
First, the most common path for immigration for Chinese nationals is through a student visa or H1-B visa for skilled workers. But travel restrictions during the early months of the pandemic temporarily stalled migration from China. Immigrant visas are out of reach for many Chinese nationals without family or vocation-based preferences, and tourist visas require a personal interview with a U.S. consulate to gauge the likelihood of the traveler returning to China.
Social media tutorials
Second, with the legal routes for immigration difficult to follow, social media accounts have outlined alternatives for Chinese who feel an urgent need to emigrate. Accounts on Douyin, the TikTok clone available in mainland China, document locations open for visa-free travel by Chinese passport holders. On TikTok itself, migrants could find information on where to cross the border, as well as information about transportation and smugglers, commonly known as “snakeheads,” who are experienced with bringing migrants on the journey north.
With virtual private networks, immigrants can also gather information from U.S. apps such as X, YouTube, Facebook and other sites that are otherwise blocked by Chinese censors.
Inspired by social media posts that both offer practical guides and celebrate the journey, thousands of Chinese migrants have been flying to Ecuador, which allows visa-free travel for Chinese citizens, and then making their way over land to the U.S.-Mexican border.
This journey involves trekking through the Darien Gap, which despite its notoriety as a dangerous crossing has become an increasingly common route for migrants from Venezuela, Colombia and all over the world.
In addition to information about crossing the Darien Gap, these social media posts highlight the best places to cross the border. This has led to a large share of Chinese asylum seekers following the same path to Mexico’s Baja California to cross the border near San Diego.
Chinese migration to US is nothing new
The rapid increase in numbers and the ease of accessing information via social media on their smartphones are new innovations. But there is a longer history of Chinese migration to the U.S. over the southern border – and at the hands of smugglers.
From 1882 to 1943, the United States banned all immigration by male Chinese laborers and most Chinese women. A combination of economic competition and racist concerns about Chinese culture and assimilability ensured that the Chinese would be the first ethnic group to enter the United States illegally.
With legal options for arrival eliminated, some Chinese migrants took advantage of the relative ease of movement between the U.S. and Mexico during those years. While some migrants adopted Mexican names and spoke enough Spanish to pass as migrant workers, others used borrowed identities or paperwork from Chinese people with a right of entry, like U.S.-born citizens. Similarly to what we are seeing today, it was middle- and working-class Chinese who more frequently turned to illegal means. Those with money and education were able to circumvent the law by arriving as students or members of the merchant class, both exceptions to the exclusion law.
Though these Chinese exclusion laws officially ended in 1943, restrictions on migration from Asia continued until Congress revised U.S. immigration law in the Hart-Celler Act in 1965. New priorities for immigrant visas that stressed vocational skills as well as family reunification, alongside then Chinese leader Deng Xiaoping’s policies of “reform and opening,” helped many Chinese migrants make their way legally to the U.S. in the 1980s and 1990s.
Even after the restrictive immigration laws ended, Chinese migrants without the education or family connections often needed for U.S. visas continued to take dangerous routes with the help of “snakeheads.”
One notorious incident occurred in 1993, when a ship called the Golden Venture ran aground near New York, resulting in the drowning deaths of 10 Chinese migrants and the arrest and conviction of the snakeheads attempting to smuggle hundreds of Chinese migrants into the United States.
Existing tensions
Though there is plenty of precedent for Chinese migrants arriving without documentation, Chinese asylum seekers have better odds of success than many of the other migrants making the dangerous journey north.
An estimated 55% of Chinese asylum seekers are successful in making their claims, often citing political oppression and lack of religious freedom in China as motivations. By contrast, only 29% of Venezuelans seeking asylum in the U.S. have their claim granted, and the number is even lower for Colombians, at 19%.
The new halt on the migratory highway from the south has affected thousands of new migrants seeking refuge in the U.S. But the mix of push factors from their home country and encouragement on social media means that Chinese migrants will continue to seek routes to America.
And with both migration and the perceived threat from China likely to be features of the upcoming U.S. election, there is a risk that increased Chinese migration could become politicized, leaning further into existing tensions between Washington and Beijing.
Meredith Oyen does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.
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Is the National Guard a solution to school violence?
School board members in one Massachusetts district have called for the National Guard to address student misbehavior. Does their request have merit? A…
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Every now and then, an elected official will suggest bringing in the National Guard to deal with violence that seems out of control.
A city council member in Washington suggested doing so in 2023 to combat the city’s rising violence. So did a Pennsylvania representative concerned about violence in Philadelphia in 2022.
In February 2024, officials in Massachusetts requested the National Guard be deployed to a more unexpected location – to a high school.
Brockton High School has been struggling with student fights, drug use and disrespect toward staff. One school staffer said she was trampled by a crowd rushing to see a fight. Many teachers call in sick to work each day, leaving the school understaffed.
As a researcher who studies school discipline, I know Brockton’s situation is part of a national trend of principals and teachers who have been struggling to deal with perceived increases in student misbehavior since the pandemic.
A review of how the National Guard has been deployed to schools in the past shows the guard can provide service to schools in cases of exceptional need. Yet, doing so does not always end well.
How have schools used the National Guard before?
In 1957, the National Guard blocked nine Black students’ attempts to desegregate Central High School in Little Rock, Arkansas. While the governor claimed this was for safety, the National Guard effectively delayed desegregation of the school – as did the mobs of white individuals outside. Ironically, weeks later, the National Guard and the U.S. Army would enforce integration and the safety of the “Little Rock Nine” on orders from President Dwight Eisenhower.
One of the most tragic cases of the National Guard in an educational setting came in 1970 at Kent State University. The National Guard was brought to campus to respond to protests over American involvement in the Vietnam War. The guardsmen fatally shot four students.
In 2012, then-Sen. Barbara Boxer, a Democrat from California, proposed funding to use the National Guard to provide school security in the wake of the Sandy Hook school shooting. The bill was not passed.
More recently, the National Guard filled teacher shortages in New Mexico’s K-12 schools during the quarantines and sickness of the pandemic. While the idea did not catch on nationally, teachers and school personnel in New Mexico generally reported positive experiences.
Can the National Guard address school discipline?
The National Guard’s mission includes responding to domestic emergencies. Members of the guard are part-time service members who maintain civilian lives. Some are students themselves in colleges and universities. Does this mission and training position the National Guard to respond to incidents of student misbehavior and school violence?
On the one hand, New Mexico’s pandemic experience shows the National Guard could be a stopgap to staffing shortages in unusual circumstances. Similarly, the guards’ eventual role in ensuring student safety during school desegregation in Arkansas demonstrates their potential to address exceptional cases in schools, such as racially motivated mob violence. And, of course, many schools have had military personnel teaching and mentoring through Junior ROTC programs for years.
Those seeking to bring the National Guard to Brockton High School have made similar arguments. They note that staffing shortages have contributed to behavior problems.
One school board member stated: “I know that the first thought that comes to mind when you hear ‘National Guard’ is uniform and arms, and that’s not the case. They’re people like us. They’re educated. They’re trained, and we just need their assistance right now. … We need more staff to support our staff and help the students learn (and) have a safe environment.”
Yet, there are reasons to question whether calls for the National Guard are the best way to address school misconduct and behavior. First, the National Guard is a temporary measure that does little to address the underlying causes of student misbehavior and school violence.
Research has shown that students benefit from effective teaching, meaningful and sustained relationships with school personnel and positive school environments. Such educative and supportive environments have been linked to safer schools. National Guard members are not trained as educators or counselors and, as a temporary measure, would not remain in the school to establish durable relationships with students.
What is more, a military presence – particularly if uniformed or armed – may make students feel less welcome at school or escalate situations.
Schools have already seen an increase in militarization. For example, school police departments have gone so far as to acquire grenade launchers and mine-resistant armored vehicles.
Research has found that school police make students more likely to be suspended and to be arrested. Similarly, while a National Guard presence may address misbehavior temporarily, their presence could similarly result in students experiencing punitive or exclusionary responses to behavior.
Students deserve a solution other than the guard
School violence and disruptions are serious problems that can harm students. Unfortunately, schools and educators have increasingly viewed student misbehavior as a problem to be dealt with through suspensions and police involvement.
A number of people – from the NAACP to the local mayor and other members of the school board – have criticized Brockton’s request for the National Guard. Governor Maura Healey has said she will not deploy the guard to the school.
However, the case of Brockton High School points to real needs. Educators there, like in other schools nationally, are facing a tough situation and perceive a lack of support and resources.
Many schools need more teachers and staff. Students need access to mentors and counselors. With these resources, schools can better ensure educators are able to do their jobs without military intervention.
F. Chris Curran has received funding from the US Department of Justice, the Bureau of Justice Assistance, and the American Civil Liberties Union for work on school safety and discipline.
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Rand Paul Teases Senate GOP Leader Run – Musk Says “I Would Support”
Rand Paul Teases Senate GOP Leader Run – Musk Says "I Would Support"
Republican Kentucky Senator Rand Paul on Friday hinted that he may jump…
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Republican Kentucky Senator Rand Paul on Friday hinted that he may jump into the race to become the next Senate GOP leader, and Elon Musk was quick to support the idea. Republicans must find a successor for periodically malfunctioning Mitch McConnell, who recently announced he'll step down in November, though intending to keep his Senate seat until his term ends in January 2027, when he'd be within weeks of turning 86.
So far, the announced field consists of two quintessential establishment types: John Cornyn of Texas and John Thune of South Dakota. While John Barrasso's name had been thrown around as one of "The Three Johns" considered top contenders, the Wyoming senator on Tuesday said he'll instead seek the number two slot as party whip.
Paul used X to tease his potential bid for the position which -- if the GOP takes back the upper chamber in November -- could graduate from Minority Leader to Majority Leader. He started by telling his 5.1 million followers he'd had lots of people asking him about his interest in running...
Thousands of people have been asking if I'd run for Senate leadership...
— Rand Paul (@RandPaul) March 8, 2024
...then followed up with a poll in which he predictably annihilated Cornyn and Thune, taking a 96% share as of Friday night, with the other two below 2% each.
????????️VOTE NOW ????️ ???? Who would you like to be the next Senate leader?
— Rand Paul (@RandPaul) March 8, 2024
Elon Musk was quick to back the idea of Paul as GOP leader, while daring Cornyn and Thune to follow Paul's lead by throwing their names out for consideration by the Twitter-verse X-verse.
I would support Rand Paul and suspect that other candidates will not actually run polls out of concern for the results, but let’s see if they will!
— Elon Musk (@elonmusk) March 8, 2024
Paul has been a stalwart opponent of security-state mass surveillance, foreign interventionism -- to include shoveling billions of dollars into the proxy war in Ukraine -- and out-of-control spending in general. He demonstrated the latter passion on the Senate floor this week as he ridiculed the latest kick-the-can spending package:
This bill is an insult to the American people. The earmarks are all the wasteful spending that you could ever hope to see, and it should be defeated. Read more: https://t.co/Jt8K5iucA4 pic.twitter.com/I5okd4QgDg
— Senator Rand Paul (@SenRandPaul) March 8, 2024
In February, Paul used Senate rules to force his colleagues into a grueling Super Bowl weekend of votes, as he worked to derail a $95 billion foreign aid bill. "I think we should stay here as long as it takes,” said Paul. “If it takes a week or a month, I’ll force them to stay here to discuss why they think the border of Ukraine is more important than the US border.”
Don't expect a Majority Leader Paul to ditch the filibuster -- he's been a hardy user of the legislative delay tactic. In 2013, he spoke for 13 hours to fight the nomination of John Brennan as CIA director. In 2015, he orated for 10-and-a-half-hours to oppose extension of the Patriot Act.
Among the general public, Paul is probably best known as Capitol Hill's chief tormentor of Dr. Anthony Fauci, who was director of the National Institute of Allergy and Infectious Disease during the Covid-19 pandemic. Paul says the evidence indicates the virus emerged from China's Wuhan Institute of Virology. He's accused Fauci and other members of the US government public health apparatus of evading questions about their funding of the Chinese lab's "gain of function" research, which takes natural viruses and morphs them into something more dangerous. Paul has pointedly said that Fauci committed perjury in congressional hearings and that he belongs in jail "without question."
Musk is neither the only nor the first noteworthy figure to back Paul for party leader. Just hours after McConnell announced his upcoming step-down from leadership, independent 2024 presidential candidate Robert F. Kennedy, Jr voiced his support:
Mitch McConnell, who has served in the Senate for almost 40 years, announced he'll step down this November.
— Robert F. Kennedy Jr (@RobertKennedyJr) February 28, 2024
Part of public service is about knowing when to usher in a new generation. It’s time to promote leaders in Washington, DC who won’t kowtow to the military contractors or…
In a testament to the extent to which the establishment recoils at the libertarian-minded Paul, mainstream media outlets -- which have been quick to report on other developments in the majority leader race -- pretended not to notice that Paul had signaled his interest in the job. More than 24 hours after Paul's test-the-waters tweet-fest began, not a single major outlet had brought it to the attention of their audience.
That may be his strongest endorsement yet.
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Is the National Guard a solution to school violence?
Rand Paul Teases Senate GOP Leader Run – Musk Says “I Would Support”
Chinese migration to US is nothing new – but the reasons for recent surge at Southern border are
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